Numerous therapies exist for the treatment of tumors including gene therapy, radiation therapy and chemotherapy. Of these therapies, radiation therapy is recognized as one of the most important methods of treating tumors. The objective of radiation therapy is to optimize the radiation delivered to the tumor while sparing normal tissue.
For approximately half a century, thyroid cancer has been effectively treated with 131I. Sodium iodide is preferentially taken up by thyroid cells where it is oxidized and incorporated onto tyrosine and ultimately incorporated into triiodothyronine (T3) and thyroxine (T4). Success in the procedure to effectively treat metastatic thyroid cancer is evident by the low mortality of patients treated with 131I (Spitzweg et al., 1999; Mazzaferri, (1996)).
Uptake of iodine by the thyroid is performed by a membrane-bound glycoprotein termed the sodium/iodide symporter (NIS; Dia et al., 1996). NIS has been expressed in different cell types. For example, WO 07/28175 discloses nucleic acids encoding human NIS, methods of producing NIS, probes for the purpose of diagnosing thyroid disorders, and methods of treating disease by using viral vectors to transfect cells with NIS and later ablate with radioiodine. Mandell et al., (1999) disclose retrovirus transfection and expression of the sodium iodide symporter within a range of tumor cell lines. Boland et al., (2000) disclose a method of providing conformal radiation therapy to non-thyroid cancers by gene therapy whereby the NIS gene is transferred into tumor cells by a recombinant adenovirus. The genetically modified tumor cells exhibit selective and significant uptake of 131I. Spitzweg et al., (1999; 2000 and 2001) describe NIS applications for gene therapy and in particular the potential application of NIS to treat prostate cancer. Habercorn, (2001) describes NIS gene therapy for the treatment of liver cancer. The reference teaches that transfection of non-thyroid cells with NIS results in cells capable of concentrating iodide approximately 20 to 40 fold above the plasma iodide concentration. Further, the reference teaches that a sufficient amount of radioiodine can be concentrated in transfected cells in vivo to bring about localized radiation therapy with a single dose of 131I.
The references discussed above disclose transforming tumor cells with a NIS gene by chemical transformation methods, electrical transformation methods or viral transformation methods to enable selective and significant uptake of 131I into tumor masses. A drawback of these references is that chemical, electrical and viral transformation methods are difficult to perform in-vivo. Further, in-vivo transformation of cells by viral vectors is difficult to control and thus other normal or healthy cells may be erroneously infected and transformed with genes enabling accumulation of radionuclides. Another drawback of these methods is that they are confined to target local or regional disease, that is the transformation vector must be administered in close proximity to the cells or tissue to be infected rather than administering the transformation vector to a subject at a remote location and having the vector identify and infect the tumor cells.
There is a need in the art for novel or alternative therapies for the treatment of tumors in a subject. Further, there is a need in the art for alternative radiotherapies to viral based gene therapy.
It is an object of the present invention to overcome disadvantages of the prior art.
The above object is met by a combination of the features of the main claims. The sub-claims disclose further advantageous embodiments of the invention.